Process for producing 4-carboxamido-5-cyano-2-imidazolone

ABSTRACT

A process for producing 4-carboxamido-5-cyano-2-imidazolone which comprises reacting diaminomaleonitrile with carbon dioxide in a polar solvent, optionally in the presence of a basic catalyst.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to a process for producing4-carboxamido-5-cyano-2-imidazolone represented by the formula ##STR1##More particularly, this invention relates to an improved process forproducing 4-carboxamido-5-cyano-2-imidazolone which comprises reactingdiaminomaleonitrile (hereinafter referred to as DAMN) with carbondioxide in a polar solvent, optionally in the presence of a basiccatalyst.

2. Description of the Prior Art

4-Carboxamido-5-cyano-2-imidazolone obtained by the process of thisinvention has been known to be useful as a plant browth regulatingagent, for example, for reducing the germination time of pea seeds andas an intermediate for the preparation of various pharmaceutical andagricultural agents, for example, uric acid, as described in R. A.Sanchez et al., U.S. Pat. No. 3,868,386. Further,4-carboxamido-5-cyano-2-imidazolone can be converted into resins whichare useful as textile crease and shrink-proofing agents, as described inU.S. Pat. No. 3,868,386.

Hitherto, a process for producing 4-carboxamido-5-cyano-2-imidazolonecomprising a reaction between DAMN and a water-soluble bicarbonate saltsuch as ammonium bicarbonate, potassium bicarbonate, sodium bicarbonate,etc., in aqueous alkaline media has been disclosed in, for example, U.S.Pat. No. 3,868,386. However, the above conventional process is notconsidered to be an advantageous process, in particular, from theindustrial standpoint, since the solvent used in the process is limitedto only water. That is, a polar solvent solution of DAMN obtainable froma manufacturing step of DAMN cannot be used directly in the process forproducing 4-carboxamido-5-cyano-2-imidazolone taught in the above priorart, and in addition, the use of an aqueous solution of DAMN is notadvantageous due to the fact that the solubility of DAMN in water is low(about 0.6% at room temperature) and that the aqueous solution of DAMNtends to form a tar-like polymer due to the polymerization of HCN duringthe storage of the solution for a prolonged period of time.

DETAILED DESCRIPTION OF THE INVENTION

As a result of extensive study on a process for producing4-carboxamido-5-cyano-2-imidazolone which can be used advantageously onan industrial scale, it was found that the above compound can beobtained easily in high yield by reacting DAMN with carbon dioxide in apolar solvent, optionally in the presence of a basic catalyst.

At present, the accumulation of carbon dioxide in the air due to therapid consumption of a large amount of organic materials in industry inrecent years has been one of serious problems from the standpoint ofambient pollutions and thus the conversion of carbon dioxide into usefulorganic materials has become one of important social requirements as ameans of recovering carbon dioxide. In view of the above fact, theprocess of this invention is advantageous in converting carbon dioxideinto useful organic compounds, particularly in fixing carbon dioxide asan organic compound having C-N bonds.

The starting material DAMN is well known in the art, for example, asdisclosed in U.S. Pat. No. 3,701,797 and can easily be prepared fromhydrogen cyanide.

In carrying out the process of this invention, the starting materialDAMN is dissolved in a polar solvent. The concentration of DAMN in apolar solvent is not critical and can vary depending upon the type ofthe polar solvent used and, partly, upon the reaction temperature used.Generally, any concentration less than the maximum solubility of DAMN inthe specific polar solvent at the specific reaction temperature employedin the reaction can be used, but use of too low concentrations of DAMNin the polar solvent would not be preferred from the economicalstandpoint since it requires a large volume of polar solvents. Forexample, 1 g of DAMN can be dissolved at room temperature in more thanabout 3 ml of dimethyl sulfoxide which is a typical example of the polarsolvent used in the present invention.

Examples of polar solvents which can be used in the present inventionare dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), alcoholshaving 1 to 4 carbon atoms such as methanol, ethanol, n-propanol,iso-propanol, n-butanol, sec-butanol, tert-butanol, etc., ethers such astetrahydrofuran, dioxane, diethyl ether, dimethoxyethane, etc.,pyridine, acetonitrile, ethyl acetate and the like. Of these solvents,dimethyl sulfoxide and N,N-dimethylformamide are preferred since theycan form complexes (solvate compounds) with4-carboxamido-5-cyano-2-imidazolone as a precipitate which can beconveniently purified by recrystallization before isolating the desired4-carboxamido-5-cyano-2-imidazolone, as described hereinafter in detail.

The reaction between DAMN in a polar solvent and carbon dioxide can beconveniently achieved by a conventional technique, for example, bybubbling or blowing a carbon dioxide gas in the solution of DAMN,preferably with stirring. Alternatively, solid carbon dioxide (dry ice)can be used as a CO₂ source preferably in such a manner that dry ice isnot directly contacted with the reaction mixture. Generally, thereaction proceeds smoothly at a temperature of from about 0° C to about60° C, preferably at a temperature of from room temperature (about 20° -30° C) to about 40° C, while blowing a carbon dioxide gas into thesolution of DAMN in a polar solvent or adding a predetermined amount ofdry ice, preferably contained in a separate vessel, to a solution ofDAMN in a polar solvent. However, it should be noted that the reactioncan also be carried out at a temperature outside the above range, forexample, at a temperature below about 0° C in such an instance that dryice is used or one desires to dissolve a large amount of carbon dioxidein a polar solvent to ensure a smooth reaction (the lower the reactiontemperature, the higher is the solubility of carbon dioxide in a polarsolvent).

The reaction can be carried out under atmospheric pressure or underpressurized conditions (autogeneous pressure) in either open vessels orclosed vessels. Also, the reaction in a closed vessel can be carried outunder either atmospheric pressure or autogeneous pressure which varieswith the amount of carbon dioxide used but is generally about 2 to about3 atms.

As is apparent to one skilled in the art, the reaction of DAMN andcarbon dioxide to form 4-carboxamido-5-cyano-2-imidazolone requirestheoretically an equimolar amount of reactants and, therefore, theamount of carbon dioxide required in the reaction can easily bedetermined from the amount of DAMN used. However, carbon dioxide ispreferably used in an excess amount relative to the amount of DAMN toensure that all the reactant DAMN used in the reaction is converted into4-carboxamido-5-cyano-2-imidazolone. Generally, about 2 to 6 moles ofcarbon dioxide per mole of DAMN is sufficient in a closed vesselreaction. When carbon dioxide gas is blown or bubbled in an open vesselreaction, the rate of blowing or bubbling can freely be varied dependingupon the scale of the reaction, the concentration of DAMN in the polarsolvent, etc. In a small scale laboratory reaction, for example, carbondioxide gas can be blown at a rate of about 3 ml/minute.

In an alternative procedure, the reaction between DAMN and carbondioxide can be advantageously carried out in the presence of a basiccatalyst. The use of the basic catalyst is not essential, but ispreferred in order to ensure a smooth reaction between DAMN and carbondioxide thereby shortening the reaction time and increasing the yield ofthe desired compound.

Examples of basic catalysts which can be used in the process of thisinvention are tertiary amines such as trialkylamines having 1 to 4carbon atoms in each of the alkyl moieties thereof such astrimethylamine, triethylamine, etc., triethylenediamine,hexamethylenetetramine, N-methylmorpholine, pyridine, and the like,basic inorganic salts such as sodium cyanide and the like, and ammoniasuch as aqueous ammonia, for example, about 28% to 30% aqeuous ammoniawhich can be commercially available, etc. As is apparent from theforegoing, pyridine serves as both the polar solvent and the basiccatalyst.

The basic catalyst can be used in an amount of from about 0.1 to about 1mole per mole of DAMN.

The reaction system is not necessarily anhydrous and a small amount ofwater contained in alcohols as polar solvents and in aqueous ammonia asbasic catalysts generally does not adversely affect the reaction betweenDAMN and carbon dioxide.

In the process of this invention, carbon dioxide is not necessarily pureCO₂ and any exhaust gas containing a substantial amount of CO₂ may alsobe used. However, from the industrial standpoint, a substantially purecarbon dioxide is advantageously used.

The time required for completing the reaction varies mainly dependingupon the reaction temperature, i.e., the temperature of the solution ofDAMN in a polar solvent, the concentration of the DAMN in a polarsolvent, the blowing rate of carbon dioxide gas as well as the type ofpolar solvents used and the presence or absence of catalysts, etc., butgenerally the reaction can be continued until no appreciable amount ofunreacted DAMN remains in the reaction mixture. The reaction can beterminated when no further precipitation of the product occurs in thereaction system. Generally, a reaction time of about 2 to about 100hours would be sufficient in most instances.

4-Carboxamido-5-cyano-2-imidazolone produced by the process of thisinvention can form a complex or solvate with the solvent used and alsocan form a salt with a base used as a basic catalyst in the reaction andthe present invention also includes within its scope a process forproducing such complexes and salts. Free4-carboxamido-5-cyano-2-imidazolone can easily be obtained from theabove complex by merely recrystallizing the complex from water.Similarly, free 4-carboxamido-5-cyano-2-imidazolone can be obtained fromthe salt by recrystallizing the salt from water which preferablycontains an acid in an amount sufficient to neutralize the base.However, the acid is not necessarily required for obtaining free4-carboxamido-5-cyano-2-imidazolone, in particular, from a salt with atrialkylamine. Examples of acids which can be used for this purpose areinorganic acids such as hydrochloric acid, sulfuric acid and the like.

When a basic catalyst is used in the process of this invention, either apolar solvent or a base having a higher affinity to4-carboxamido-5-cyano-2-imidazolone can form a complex or a salt,respectively. For example, dimethyl sulfoxide has an affinity higherthan triethylamine and, thus, the product obtained from a reactionmixture containing dimethyl sulfoxide and triethylamine is generally acomplex with dimethyl sulfoxide rather than a salt with triethylamine.

The present invention is further illustrated by the following Examples,but they are not to be construed as limiting the scope of thisinvention. Unless otherwise indicated, all percentages used therein areby weight.

EXAMPLE 1

10.8 g of diaminomaleonitrile and 10.1 g of triethylamine were dissolvedin 150 ml of N,N-dimethylformamide and carbon dioxide gas was then blowninto the solution at a rate of about 3 ml to 30 ml/minute whilemaintaining the solution at a temperature of 0° C for 1 hour and then ata temperature of 40° C for 38 hours. After completion of the reaction,300 ml of diethyl ether was added to the reaction mixture, and 22.1 g ofa precipitate of a complex of 4-carboxamido-5-cyano-2-imidazolone andN,N-dimethylformamide was separated by filtration. The complex thusobtained was found to decompose at a temperature higher than 250° C.

Elementary Analysis: Calcd. for C₈ H₁₁ N₅ O₃ : C, 42.67; H, 4.92; N,31.10%. Found: C, 42.53; H, 4.85; N, 31.00%.

NMR Spectrum (DMSO-d₆)δ: 11.25 (bs, 2H), 7.97 (s, 1H), 7.60 (bs, 2H),2.90 (s, 3H), 2.73 (s, 3H).

IR Absorption Spectrum (Nujol) cm⁻¹ : 3375, 3150, 2240, 1720, 1660,1610, 1462, 1410, 1104, 1017, 816, 747, 707.

The complex thus obtained was then recrystallized from water to give14.8 g (98% yield) of 4-carboxamido-5-cyano-2-imidazolone as whitecrystals. The product was found to decompose at a temperature higherthan 300° C.

Elementary Analysis: Calcd. for C₅ H₄ N₄ O₂ : C, 39.48; H, 2,65; N,36.83%. Found: C, 39.38; H, 2.66; N, 36.88%.

The IR, UV and NMR absorption spectra of4-carboxamido-5-cyano-2-imidazolone thus obtained were found to be quiteconsistent with those of an authentic sample disclosed in U.S. Pat. No.3,868,386.

EXAMPLE 2

10.8 g of diaminomaleonitrile and 10.1 g of triethylamine were dissolvedin 100 ml of dimethyl sulfoxide and the solution was stirred at roomtemperature for 22 hours while blowing carbon dioxide gas. 20 ml ofethanol and 300 ml of diethyl ether were then added to the reactionmixture to obtain 23.0 g (100% yield) of a 1:1 complex of4-carboxamido-5-cyano-2-imidazolone and dimethyl sulfoxide. The productthus obtained was then recrystallized from dimethyl sulfoxide andethanol and found to decompose at a temperature near 200° C.

Elemental Analysis: Calcd. for C₇ H₁₀ N₄ O₃ S: C, 36.52; H, 4.38; N,24.33; S, 13.93%. Found: C, 36.62; H, 4.44; N, 24.48; S, 14.15%.

The complex obtained above was recrystallized from water to give 13.6 g(89% yield) of 4-carboxamido-5-cyano-2-imidazolone.

EXAMPLE 3

10.8 g of diaminomaleonitrile and 1.0 g of triethylamine were dissolvedin 100 ml of dimethyl sulfoxide and the resulting solution was stirredat a temperature of 40° C for 22 hours while blowing carbon dioxide gasinto the solution. The resulting reaction mixture was then worked up inthe same manner as described in Example 2 to obtain 15.8 g (69% yield)of a 1:1 complex of 4-carboxamido-5-cyano-2-imidazolone and dimethylsulfoxide. Recrystallization of the complex thus obtained from watergave 4-carboxamido-5-cyano-2-imidazolone.

EXAMPLE 4

10.8 g of diaminomaleonitrile and 0.49 g of sodium cyanide weredissolved in 100 ml of dimethyl sulfoxide and the resulting solution wasstirred at room temperature for 22 hours while blowing carbon dioxidegas into the solution. The reaction mixture was then worked up in thesame manner as described in Example 2 and the precipitate formed waswashed with a small amount of ethanol to obtain 21.6 g (94% yield) of a1:1 complex of 4-carboxamido-5-cyano-2-imidazolone and dimethylsulfoxide.

Recrystallization of the complex thus obtained from water gave4-carboxamido-5-cyano-2-imidazolone.

EXAMPLES 5 to 10

10.8 g of diaminomaleonitrile was reacted with carbon dioxide gas usingeach of the solvents and the bases indicated in Table below under thereaction conditions also indicated in Table below. In each instance,4-carboxamido-5-cyano-2-imidazolone or a complex or salt thereof wasobtained in the yield shown in Table.

The triethylamine salt of 4-carboxamido-5-cyano-2-imidazolone obtainedin this example was found to turn into a red-brown colored product at atemperature higher than 190° C and decomposed at a temperature higherthan 250° C. This complex had the following characteristics.

NMR Spectrum (DMSO-d₆)δ: 8.2 (2H), 7.5 (2H), 2.68 (q, J=7Hz, 6H), 1.03(t, J=7Hz, 9H).

IR Absorption Spectrum (KBr disc) cm⁻¹ : 3450, 3220, 2670, 2235, 1720,1602, 1445, 1300, 1030, 750, 703.

                                      Table                                       __________________________________________________________________________                                Reaction                                                                             Reaction       Yield                       Example                                                                            Polar Solvent                                                                           Basic Catalyst                                                                             Temp. (° C)                                                                   Time (hrs.)                                                                         Product  (%)                         __________________________________________________________________________    5    Acetonitrile                                                                            Triethylamine (10.1 g)                                                                     40     20    Triethylamine                                                                          90                               (200 ml)                            Salt of CCI*                         6    Pyridine (100 ml)                                                                       --           40     43    CCI      74                          7    Ethanol (150 ml)                                                                        Triethylamine (10.1 g)                                                                     40     18    DMSO Complex                                                                           70                                                                   of CCI                               8    Dimethyl Sulfoxide                                                                      28% Aq. Ammonia (5.5 g)                                                                    40     22    DMSO Complex                                                                           95                               (100 ml)                            of CCI                               9    Tetrahydrofuran                                                                         Triethylamine (10.1 g)                                                                      0      5    Triethylamine                                                                          51                               (200 ml)                            Salt of CCI                          10   Dimethyl Sulfoxide                                                                      --           40     67    DMSO Complex                                                                           16                               (100 ml)                            of CCI                               __________________________________________________________________________     *CCI = 4-carboxamido-5-cyano-2-imidazolone                               

EXAMPLE 11

30 ml of acetonitrile and 0.310 g (3.06 m moles) of triethylamine werecharged into a 200 ml-round bottle flask equipped with a 250 ml-gasburet and the reaction system was purged with a carbon dioxide gas underatmospheric pressure. 0.330 g (3.15 m moles) of diaminomaleonitrile wasthen added to the reaction system and a CO₂ absorption rate wasdetermined by the gas buret while stirring and found that 39%, 66% and90% of CO₂ gas charged had been absorbed 36 minutes, 90 minutes and 233minutes, respectively, after initiation of the reaction. Then, about 100ml of diethyl ether was added to the reaction mixture to obtain 0.650 g(82% yield) of a salt of 4-carboxamido-5-cyano-2-imidazolone andtriethylamine as a precipitate. The salt thus obtained was dissolved indimethyl sulfoxide and diethyl ether was added to the resulting solutionto precipitate 0.570 g (74% yield) of a complex of 4-carboxamido-5-cyano-2-imidazolone and dimethyl sulfoxide.

Recrystallization of the complex thus obtained from water gave4-carboxamido-5-cyano-2-imidazolone.

EXAMPLE 12

1.08 g of diaminomaleonitrile, 1.01 g of triethylamine and 10 ml ofdimethyl sulfoxide were charged into a 100 ml pressure-resistant glasstube. 1.10 g of dry ice was placed in a separate test tube which wasthen placed in the above pressure-resistant glass tube in such a mannerthat dry ice would not contact directly with the reaction mixture. Theglass tube was then sealed and the reaction was conducted at roomtemperature for 20 hours. After completion of the reaction, the reactionmixture was worked up in the same manner as described in Example 2 toobtain 2.24 g (97% yield) of a complex of4-carboxamido-5-cyano-2-imidazolone and dimethyl sulfoxide.

Recrystallization of the complex thus obtained from water gave4-carboxamido-5-cyano-2-imidazolone.

While the invention has been described in detail and with reference tospecific embodiments thereof, it will be apparent to one skilled in theart that various modifications and changes can be made therein withoutdeparting from the spirit and scope thereof.

What is claimed is:
 1. A process for producing4-carboxamido-5-cyano-2-imidazolone which comprises reactingdiaminomaleonitrile in the presence of a basic catalyst selected fromthe group consisting of a trialkylamine having 1 to 4 carbon atoms ineach of the alkyl moieties thereof, triethylenediamine,hexamethylenetetramine, N-methylmorpholine, and pyridine with carbondioxide in an organic polar solvent selected from the group consistingof dimethyl sulfoxide, N, N-dimethylformamide, an alcohol having 1 to 4carbon atoms, tetrahydrofuran, dioxane, diethyl ether, dimethoxyethane,pyridine, acetonitrile and ethyl acetate at a temperature of from about0° C to about 60° C.
 2. The process according to claim 1, wherein saidreaction is conducted in the presence of a basic catalyst in an amountof from about 0.1 mole to about 1 mole per mole of saiddiaminomaleonitrile.